Summary Tuberculosis (TB) is the leading cause of mortality from an infectious disease worldwide. Inadequate adherence and suboptimal TB drug exposure contribute to treatment failure and the emergence of drug resistance. While adherence questionnaires are utilized to monitor TB therapy intake, their validity is limited by recall bias. Single plasma levels are also used to assess drug exposure, but they estimate only a small window of exposure. Hair assays has been utilized previously to monitor adherence and exposure to chronically administered medications in conditions such as epilepsy and HIV. Similarly, hair assays of TB drugs may be a low-cost and noninvasive, alternative method for assessing adherence and exposure to TB drugs among HIV-infected and uninfected adults and children. The overall goal of this proposal is to evaluate whether TB drug concentrations in hair correlate with TB treatment outcomes in a large cohort of patients with TB. The overarching hypothesis is that hair concentrations of isoniazid (INH) and pyrazinamide (PZA) will be strong predictors of TB treatment outcomes (e.g. culture conversion in 2 months, treatment success, recurrence, and death). Our specific aims are: 1) To clinically validate assays for measuring first-line TB drugs in small hair samples; 2) To assess the incremental value of hair drug concentrations in predicting clinical outcomes among HIV-infected and -uninfected adults and children receiving 1st line TB drugs. The study will leverage specimens and clinical data already collected from an ongoing multicenter prospective observational study called ?Cohort for TB Research by the Indo-US Medical Partnership? (C TRIUMPH) that incorporated hair collection at months 1, 5 and 6 on TB treatment. We will build on existing successful Indo-US collaborations between Johns Hopkins University, USA, University of California, San Francisco (UCSF) USA, National Institute of Research in Tuberculosis, Chennai, India and BJ Government Medical College, Pune, India.